Therapeutic and antiproteinuric effects of salvianolic acid A in combined with low-dose prednisone in minimal change disease rats: Involvement of PPARγ/Angptl4 and Nrf2/HO-1 pathways.

Abstract

Danshen (Salvia miltiorrhiza) and prednisone are extensively applied in the treatment of kidney disease. Salvianolic acid A (SAA), the major biologically active component of Danshen, which has various biological effects. Our previous findings have demonstrated the renoprotective effect of SAA in various kidney disease rodent models. Here, we explore the therapeutic potential and possible mechanisms of SAA in combination with low-dose prednisone in adriamycin (ADR)-induced minimal change disease (MCD) rat model and mouse podocyte injury cell model. SAA was injected via tail vein at 10 mg/kg/day and prednisone at 5 mg/kg/day via gavage. Each drug was administered daily alone or in combination for 3 weeks. Combination therapy showed significant therapeutic efficacy as manifested by relieved urinary proteins, improved blood biochemical indicators including serum total protein, albumin, triglyceride, cholesterol, the indices of renal function i.e. blood urea nitrogen and serum creatinine levels, and ameliorated pathological lesions. Particularly, co-administration showed a significant anti-proteinuria effect in MCD rats. Further studies suggested that co-administration effectively ameliorated the podocyte injury as indicated by the reduction of podocyte foot processes fusion, up-regulation of synaptopodin and down-regulation of desmin. These beneficial effects are accompanied by activation of the Nrf2/HO-1 and PPARγ/Angptl4 pathways in vivo, and the effect of SAA on PPARγ/Angptl4 is also demonstrated in vitro. These findings suggested that SAA exerted podocyte-protection against MCD injury through PPARγ/Angptl4 and Nrf2/HO-1 pathways, and combined with low-dose prednisone possessed a significant anti-proteinuria and therapeutic effects in MCD rats.

• Authors: Xuekai Wang, Dong Qi, Fenghua Fu, Xin Li, Yue Liu, Kai Ji, Zhenfang Gao, Linlin Kong, Chen Yu, Hua Xie, Guang Yue, Hui Zhu, Ke Liu, Huaying Fan
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 858 Pg. 172342 (Sep 05 2019) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 31129156 (Publication Type: Journal Article)
• Copyright: Copyright © 2019. Published by Elsevier B.V.

Chemical References

• ANGPTL4 protein, rat
• Angiopoietin-Like Protein 4
• Caffeic Acids
• Lactates
• NF-E2-Related Factor 2
• Nfe2l2 protein, rat
• PPAR gamma
• salvianolic acid A
• Heme Oxygenase (Decyclizing)
• Hmox1 protein, rat
• Prednisone

Topics

• Angiopoietin-Like Protein 4 (metabolism)
• Animals
• Caffeic Acids (pharmacology, therapeutic use)
• Drug Interactions
• Heme Oxygenase (Decyclizing) (metabolism)
• Lactates (pharmacology, therapeutic use)
• Male
• Mice
• NF-E2-Related Factor 2 (metabolism)
• Oxidative Stress (drug effects)
• PPAR gamma (metabolism)
• Podocytes (drug effects, pathology)
• Prednisone (pharmacology, therapeutic use)
• Proteinuria (drug therapy, metabolism, pathology)
• Rats